cyclophosphamide and fludarabine followed by interleukin-2 gene-modified tumor infiltrating lymphocytes in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: rationale: drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells. purpose: this phase i/ii trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase i is closed to accrual 3/29/06).

objectives: primary * determine the survival of patients with metastatic melanoma administered interleukin-2 gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine. * compare survival results with prior surgery branch studies using adoptive cell therapy without the interleukin-2 retroviral vector (sbil-2) gene. secondary * determine clinical tumor regression in patients administered interleukin-2 gene-modified til after cyclophosphamide and fludarabine followed by interleukin-2. * determine the toxicity profile of this regimen in these patients. outline: * phase i (closed to accrual as of 3/29/06): * harvest: til are harvested, transduced with il-2 gene, and expanded in vitro over a period of approximately 4 weeks. * nonmyeloablative preparative regimen (chemotherapy): patients receive cyclophosphamide iv over 1 hour on days -7 and -6 and fludarabine iv over 30 minutes on days -5 to -1. * lymphocyte administration: patients receive il-2 gene-transduced til iv over 20-30 minutes on day 0. they also receive high-dose il-2 iv over 15 minutes every 8 hours on days 0 -5 (maximum 15 doses). beginning 1-2 days after lymphocyte administration, patients receive filgrastim (g-csf) subcutaneously (sc) daily, , until blood counts recover. * retreatment: patients are re-evaluated every 4-6 weeks. retreatment depends on disease status after each regimen. patients with dose-limiting toxicity do not receive further treatment. * no response: patients with stable disease or disease progression after the initial treatment are followed or removed from the study. * partial response: patients with a partial or minor response after the initial treatment may receive retreatment, approximately 2-4 weeks later, with chemotherapy, il-2 gene-transduced til, immunization, and high-dose il-2 as above, every 4-6 weeks for up to 2 courses provided at least a partial response is documented after each regimen. * complete response: patients with a complete response receive no further treatment. * phase ii: patients receive treatment and retreatment as in phase i with the mtd of il-2 gene-transduced til. patients are followed every 3-6 weeks in the absence disease progression. projected accrual: a total of 33 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of melanoma * metastatic disease * refractory to standard therapy including high-dose interleukin-2 (il-2) therapy * evaluable disease * patients may enroll at the cell infusion stage provided they have tumor available for biopsy or expandable sbil-2-transduced tumor infiltrating lymphocytes available * progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed * symptomatic cns lesions allowed provided immediate active treatment for symptomatic lesions has been completed patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * more than 3 months hematopoietic * absolute neutrophil count greater than 1,000/mm\^3 * wbc greater than 3,000/mm\^3 * lymphocyte count greater than 500/mm\^3 * platelet count greater than 100,000/mm\^3 * hemoglobin greater than 8.0 g/dl * no coagulation disorder hepatic * bilirubin no greater than 2.0 mg/dl (less than 3.0 mg/dl in patients with gilbert's syndrome) * ast/alt less than 3 times upper limit of normal * hepatitis b surface antigen negative * hepatitis c virus negative renal * creatinine no greater than 1.6 mg/dl cardiovascular * no myocardial infarction * no cardiac arrhythmias * no abnormal stress thallium or comparable test * lvef \> 45% and normal stress cardiac test in patients with the following criteria: * 50 years old or greater * history of ekg abnormalities, symptoms of cardiac ischemia or arrhythmias * no major cardiovascular illness pulmonary * no obstructive or restrictive pulmonary disease * no major respiratory illness * fev_1 \> 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction immunologic * hiv negative * no prior severe immediate hypersensitivity reaction * no primary or secondary immunodeficiency * no active systemic infection * no concurrent opportunistic infection * no major immune system illness other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 4 months after study therapy * must sign a durable power of attorney prior concurrent therapy: biologic therapy * see disease characteristics * no prior anti-cytotoxic t-lymphocyte antibody-4 antibody (ctla-4) allowed unless post-mdx010 treatment and colonoscopy with colonic biopsies are normal chemotherapy * recovered from prior chemotherapy endocrine therapy * no concurrent steroids radiotherapy * recovered from prior radiotherapy surgery * not specified other * more than 4 weeks since prior systemic therapy

Keywords: stage iv melanoma recurrent melanoma